Multiple Myeloma Supportive Care

Sagar Lonial, MD: One of the things that I think has become even more important as myeloma patients are living longer is trying to understand how to optimally support them during their therapy and prevent the emergence of long-term adverse events. And peripheral neuropathy is probably the biggest one. We now know we make dose adjustments and dose modifications earlier in the course of therapy. Patients that are on, for instance, IMiD maintenance for a longer time now—2 years, 3 years, or 5 years—we’re starting to see the emergence of some mild grade 1 peripheral neuropathy in those patients, as well. And so, just making sure you’re paying attention to those kinds of events and adjusting the dose of medications, if needed, I think is actually really important.

The other area that’s probably growing relatively rapidly is bone health. We’ve known that bisphosphonates like zoledronic acid and pamidronate have been very active at preventing skeletal events. We also know that the proteasome inhibitors—bortezomib, and carfilzomib, and ixazomib—all actually protect the bone, and actually help to rebuild the bone. But there are now data on the use of the RANK ligand inhibitor, denosumab, which seems to be somewhat similar in terms of its ability to prevent skeletal-related events, but may actually be safer to use in patients with renal insufficiency—a big issue among myeloma patients. And so, I think emerging focus on bone and bone protection is another area where I think we need to pay a lot more attention.

For this specific patient, I think there are 2 areas worth focusing on. The first is the significant amount of back pain and bone pain associated with the compression fractures. And, this is somebody who we would very actively try and obtain something like kyphoplasty or vertebroplasty for, to see if we could rapidly alleviate some of their symptoms. The use of dexamethasone should actually help with pain relief as well. The use of bortezomib will actually help with pain relief, particularly in bone lesions. That will be helpful as well. And, of course, supportive therapy such as zoledronic acid or pamidronate would be also indicated in this patient. Now because of his renal insufficiency—he has got a creatinine clearance of about 32—this actually may be a patient where the use of denosumab might be an important approach, given that bisphosphonates do have some contraindications in the context of renal insufficiency.

And one of the important things to remember as you use denosumab in myeloma is that one of the most common side effects is symptomatic hypocalcemia, so making sure that patients are getting calcium and vitamin D supplementation throughout their use of denosumab might be really important as well. And then, again, there are other issues such as maintaining adequate hydration and avoidance of nonsteroidal anti-inflammatory agents. Avoidance of CT scan contrast would also be important, given that this is an older, frailer patient who doesn’t have normal renal function.

Transcript edited for clarity.

Multiple Myeloma in an Older Patient Who Develops Symptomatic Progression

December 2013

• A 77-year old African American male was diagnosed 24 months ago with stage III multiple myeloma and was not eligible for transplant based on his level of frailty
• His cytogenetics were classified as intermediate risk
• He received treatment with lenalidomide (15 mg daily) and low-dose dexamethasone

December 2015

• He reported feeling tired but continued to do well functionally
• Laboratory findings:
  • Hb, 11.4 g/dL
  • Creatinine, 1.0 mg/dL
  • M-protein rose from 0.6 g/dl→1.2 g/dl→1.5 g/dl
• Lenalidomide was increased to 25 mg daily; M-protein returned to normal

December 2016

• The patient was hospitalized 2 months ago for pneumonia and now complains of increasing back pain, fatigue, and weakness
• Laboratory findings:
  • M-protein, 2.1 g/dl
  • Serum beta-2-microglobulin, 6.2 mg/L
  • Albumin, 2.1 g/dL
  • Creatinine clearance of 32 ml/min
• Skeletal survey shows new compression fracture in the L4/L5 vertebrae
• Bone marrow biopsy shows 30% involvement by abnormal appearing plasma cells, confirmed by CD138+ IHC stain
• Performance status, ECOG 2
• The patient was treated with daratumumab, weekly subcutaneous bortezomib, and dexamethasone